Organisms have various mechanisms in order to obtain, e.g., nutrients and signal transmitters required for their vital activities, and many different transporters and receptors present on their respective cell membranes are a few examples of these mechanisms. Among them, the transport of amino acids, which are major elements constituting the living body, has been studied since the 1960s. Molecules responsible for amino acid transport have been identified starting in 1990, and approximately 30 types of dominant genes have now been identified. These transporters are broadly divided into three types, i.e., basic amino acid transporters, neutral amino acid transporters and acidic amino acid transporters, depending on the nature of amino acids to be transported. However, there are six members, including LAT1 described below, for amino acid transporters heterodimerized with CD98.
LAT1 is a sodium-independent neutral amino acid transporter which has relatively broader substrate selectivity than other transporters. LAT1 is a twelve-transmembrane protein cloned in 1998 and is present on the cell membrane surface. LAT1 is one of the six members of CD981c and forms a heterodimer when disulfide bonded with a single transmembrane protein, 4F2hc(CD98), thereby exerting amino acid transport activity. 4F2hc is a chaperone-like molecule which binds to a specific transporter for migration to the cell membrane (e.g., Yoshikatsu Kanai, Protein, Nucleic Acid and Enzyme Vol. 46, No. 5, pp. 629-637, 2001 (Non-patent Document 1)).
Until now, many cases have been reported where the LAT1/CD98 complex is highly expressed in tumor cells (Yanagida et al., Biochimica et Biophysica Acta Vol. 1514, pp. 291-302, 2001 (Non-patent Document 2), Ohno et al., Cancer Sci. Vol. 99, No. 5, pp. 1000-1007, 2008 (Non-patent Document 3), Kaira et al., Cancer Sci. Vol. 99, No. 12, pp. 2380-2386, 2008 (Non-patent Document 4), Kaira et al., Cancer Sci. Vol. 100, No. 2, pp. 249-254, 2009 (Non-patent Document 5)). Amino acids are substances indispensable for cell growth, and tumor cells appear to require more amino acids than usual because they repeatedly grow in an uncontrolled manner. For this reason, it is inferred that the expression levels of amino acid transporters are higher in tumor cells than in normal cells. It is therefore suggested that the LAT1/CD98 complex is useful as a target molecule for tumor treatment.